Microsatellite instability and high tumor mutational burden detected by next generation sequencing are concordant with loss of mismatch repair proteins by immunohistochemistry.

Impairment of DNA mismatch repair function in neoplasms can be assessed by DNA-based methods to assess for high microsatellite instability (MSI-High) or immunohistochemical (IHC) analysis to assess for deficiency of mismatch repair proteins (dMMR). Neoplasms with mismatch repair deficiency often have high tumor mutational burden (TMB-High). MSI-High, dMMR, and TMB-High are all histology agnostic biomarkers for potential therapy using immune checkpoint inhibitors (ICI).

Hyperactive neuronal networks facilitate tau spread in an Alzheimer's disease mouse model.

Pathological tau spreads throughout the brain along neuronal connections in Alzheimer's disease (AD), but the mechanisms that underlie this process are poorly understood. Given the high incidence and deleterious consequences of epileptiform activity in AD, we hypothesized neuronal hyperactivity and seizures are key factors in tau spread. To examine these interactions, we created a novel mouse model involving the cross of targeted recombination in active populations (TRAP) mice and the 5 times familial AD (5XFAD; 5X-TRAP) model allowing for the permanent fluorescent labelling of neuronal activity.

Polygenic risk scores for cardiometabolic traits demonstrate importance of ancestry for predictive precision medicine.

Polygenic risk scores (PRS) have predominantly been derived from genome-wide association studies (GWAS) conducted in European ancestry (EUR) individuals. In this study, we present an in-depth evaluation of PRS based on multi-ancestry GWAS for five cardiometabolic phenotypes in the Penn Medicine BioBank (PMBB) followed by a phenome-wide association study (PheWAS). We examine the PRS performance across all individuals and separately in African ancestry (AFR) and EUR ancestry groups.

Integumentary and musculoskeletal indications for surgery predominate in a 15-year study of search-and-rescue dogs.

Objective: Analyze data from a 15-year longitudinal study of search-and-rescue (SAR) dogs to determine the indications for surgery and evaluate whether the risk varied by breed, sex, neutering, or deployment status during 9/11.

Methods: 150 SAR dogs: 95 dogs deployed to sites from the September 11, 2001, terrorist attacks and 55 SAR dogs not deployed to these sites. Search-and-rescue dog handlers completed an annual health survey until the dog's death, or the handler withdrew from the study.